Mutagenicity of butadiene and butadiene monoxide

Meester, Conrad De; Poncelet, F.; Roberfroid, Marcel; Mercier, Michel

doi:10.1016/0006-291x(78)90676-9

Cited by 82 publications

(18 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1,2-Epoxybutene-3 (butadiene monoxide) was mutagenic in bacterial test systems (De Meester et al 1978;Hemminki et al 1980;Voogd et al 1981) and carcinogenic in mice (Van Duuren et al 1963). It is a reactive metabolite of 1,3-butadiene (butadiene) (Filser and Bolt 1984) which has also been shown to be carcinogenic.…”

Section: Introductionmentioning

confidence: 95%

Enzyme specific kinetics of 1,2-epoxybutene-3 in microsomes and cytosol from livers of mouse, rat, and man

Kreuzer¹,

Kessler²,

Welter³

et al. 1991

Arch Toxicol

View full text Add to dashboard Cite

Kinetics of the metabolism of 1,2-epoxybutene-3 (butadiene monoxide) were investigated in liver fractions of mouse, rat, and man. In these species similar enzyme characteristics were found. In microsomes, no NADPH-dependent metabolism of butadiene monoxide was detectable. Epoxide hydrolase activity was found only in microsomes. The Vmax [nmol butadiene monoxide/(mg protein x min)] was 19 in mouse, 17 in rat, and 14 in man and the apparent Km (mmol butadiene monoxide/l incubate) was 1.5 in mouse. 0.7 in rat, and 0.5 in man. Glutathione S-transferase activity was found in cytosol only, revealing first order kinetics in the measured range. The ratio Vmax/Km [(nmol butadiene monoxide x 1)/(mg protein x min x mmol of butadiene monoxide)] was 15 in mouse, 11 in rat, and 8 in man. The data obtained were used to extrapolate on the total rate of butadiene monoxide metabolism for each species in vivo: it was calculated to be 1.3 times higher in mice and 2.3 times lower in man compared to rats, when corrected for body weight.

show abstract

Section: Introductionmentioning

confidence: 95%

Enzyme specific kinetics of 1,2-epoxybutene-3 in microsomes and cytosol from livers of mouse, rat, and man

Kreuzer¹,

Kessler²,

Welter³

et al. 1991

Arch Toxicol

View full text Add to dashboard Cite

show abstract

“…Thus, two Salmonella strains, TA1535 and TA1537, were selected because the DNA sequences in the two strains are designed to detect point mutations and frameshift mutations, respectively (Mortelmans and Zeiger, 2000), and these strains were used previously to characterize BD, EB, and DEB mutagenicity (de Meester et al, 1978; Himmelstein et al, 2001; McCann et al, 1975). All experiments were carried out using the pre-incubation assay procedure as described in the literature (Mortelmans and Zeiger, 2000).…”

Section: Methodsmentioning

confidence: 99%

Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene

Liu

Zeng

et al. 2013

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

The cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene (CHB), a known in vitro metabolite of the human carcinogen 1,3-butadiene, have not previously been investigated. Because CHB can be bioactivated by alcohol dehydrogenases to yield 1-chloro-3-buten-2-one (CBO), a bifunctional alkylating agent that caused globin-chain cross-links in erythrocytes, in the present study we investigated the cytotoxic and genotoxic potential of CHB and CBO in human normal hepatocyte L02 cells using the MTT assay, the relative cloning efficiency assay and the comet assay. We also investigated the mutagenic potential of these compounds with the Ames test using Salmonella strains TA1535 and TA1537. The results provide clear evidence for CHB and CBO being both cytotoxic and genotoxic with CBO being approximately 100-fold more potent than CHB. Interestingly, CHB generated both single-strand breaks and alkali-labile sites on DNA, whereas CBO produced only alkali-labile sites. CHB did not directly result in DNA breaks, whereas CBO was capable of directly generating breaks on DNA. Interestingly, both compounds did not induce DNA cross-links as examined by the comet assay. The Ames test results showed that CHB induced point mutation but not frameshift mutation, whereas the toxic effects of CBO made it difficult to reliably assess the mutagenic potential of CBO in the two strains. Collectively, the results suggest that CHB and CBO may play a role in the mutagenicity and carcinogenicity of 1,3-butadiene.

show abstract

“…Butadiene is mutagenic in the S. typhimurium assay in the presence of metabolic activation (393,(485)(486)(487). Butadiene is a weak inducer of sister chromatid exchanges in Chinese hamster ovary cells, but only in the presence of S9 mix (488).…”

Section: Genetic and Related Cellular Effects Studiesmentioning

confidence: 98%

Aliphatic Hydrocarbons

Carreón¹,

Herrick²

2012

Patty's Toxicology

View full text Add to dashboard Cite

Aliphatic hydrocarbons are open‐chain compounds that may be saturated or unsaturated. The saturated compounds, known as paraffin hydrocarbons or alkanes , include methane and its homologs having the empirical formula C n H 2 n +2 . The unsaturated compounds fall into a number of homologous series: ( 1 ) those containing one double bond (ethylene and its homologs) and having the formula C n H 2 n are known as olefins or alkenes ; ( 2 ) those containing one triple bond (acetylene and its homologs) are called acetylenes or alkynes and have the formula C n H 2 n −2 ; ( 3 ) those having two double bonds (allene, 1,3‐butadiene and 1,4‐pentadiene represent three types) are diolefins or alkadienes and also have the formula C n H 2 n −2 ; ( 4 ) those having a large number of double or triple bonds or both double and triple bonds are named in analogous fashion as alkatrienes , alkatetraenes , alkadiynes , alkenynes , and alkadienynes . Aliphatic hydrocarbons are asphyxiants and central nervous system ( CNS ) depressants. Serious toxic effects of aliphatic hydrocarbons include asphyxia and chemical pneumonitis for many paraffins, axonal neuropathy for n ‐hexane, and cancer for 1,3‐butadiene.

show abstract

Mutagenicity of butadiene and butadiene monoxide

Cited by 82 publications

References 11 publications

Enzyme specific kinetics of 1,2-epoxybutene-3 in microsomes and cytosol from livers of mouse, rat, and man

Enzyme specific kinetics of 1,2-epoxybutene-3 in microsomes and cytosol from livers of mouse, rat, and man

Cytotoxicity, genotoxicity, and mutagenicity of 1-chloro-2-hydroxy-3-butene and 1-chloro-3-buten-2-one, two alternative metabolites of 1,3-butadiene

Aliphatic Hydrocarbons

Contact Info

Product

Resources

About